Spotlight on Tuberculosis

By Nader Fotouhi, Vice President, Pharma Research and Early Development Site Leader, Hoffmann La Roche, Nutley and Member, Scientific Advisory Board of the Boulder Peptide Society

Evidence of tubercular decay has been found in the spines of Egyptian mummies thousands of years old, and TB was common both in ancient Greece and Imperial Rome. Since that time, scientific advances, including the discovery of the TB mycobacterium and the development of new drugs and the BCG vaccine, caused TB to lessen its devastating effect. However, TB never completely let go. It is estimated that the number of cases of tuberculosis worldwide in 2012 was 8.6 million. Tuberculosis caused 1.3 million deaths, including 320 000 deaths in people with HIV. WHO estimates that about 2 billion people have latent tuberculosis infection, and more than 100 million people with latent infection will develop active disease during their lifetime. The first drug discovered over 70 years ago was Stretomycin and gave a fighting chance for survival, but faced resistance very quickly pointing to the inadequacy of single agent treatment. The first oral therapeutic regimen (6 months of rifampicin, isoniazid, pyrazinamide, and ethambutol) was discovered in the 50sw and 60s and is still used today. However, Multidrug-resistant tuberculosis, caused by M tuberculosis bacilli resistant to at least isoniazid and rifampicin, is now widespread throughout the world, with about half a million cases reported in 2012. Extensively drug-resistant tuberculosis (resistance to rifampicin, isoniazid, plus any fluoroquinolone, and at least one of three injectable second-line drugs, (amikacin, kanamycin, or capreomycin) has been reported in 92 countries. After 50 years of no drug development, two new drugs, delamanid and bedaquiline were approved and a range of novel antituberculosis drugs are in preclinical and clinical development, for drug-sensitive and drug-resistant tuberculosis. Combinations of these and existing drugs are being assessed to shorten the duration of therapy to as little as 2 months and to treat multidrug-resistant tuberculosis.